From karyotyping to array-CGH in prenatal diagnosis.

Area of Science:

• Prenatal diagnosis
• Medical genetics
• Genomic technologies

Background:

• Conventional karyotyping is a standard prenatal diagnostic technique for chromosomal anomalies, detecting up to 35% of cases with fetal ultrasound anomalies.
• Array comparative genomic hybridization (array-CGH) and SNP array are now first-tier investigations for postnatal diagnosis of congenital anomalies and intellectual disability.
• The higher detection rate and automation potential of array-CGH make it suitable for prenatal diagnosis.

Purpose of the Study:

• To review the outcomes of prenatal array-CGH studies.
• To compare the clinical relevance and detection capabilities of array-CGH versus standard karyotyping.
• To discuss the future integration of novel molecular techniques in prenatal diagnosis workflows.

Main Methods:

• Review of retrospective and prospective studies on array-CGH in prenatal diagnosis, particularly for pregnancies with ultrasound anomalies.
• Comparison of diagnostic yields between array-CGH and conventional karyotyping.
• Analysis of array-CGH findings, including variants of uncertain significance and incidental findings.

Main Results:

• Array-CGH demonstrated an increased diagnostic yield compared to karyotyping, ranging from 1-5% depending on the referral reason.
• Studies initially focused on retrospective data but have expanded to prospective applications.
• The spectrum of array-CGH detected anomalies in the prenatal setting is rapidly expanding.

Conclusions:

• Prenatal array-CGH offers a higher diagnostic yield than conventional karyotyping for detecting chromosomal anomalies.
• Increased knowledge of array-CGH findings will enhance pre- and post-test counseling for expectant parents.
• Emerging technologies like non-invasive prenatal diagnosis are expected to become integral to future prenatal diagnostic workflows.